Growth of collagen fibrils was examined in a system in which collagen monomers are generated by specific enzymic cleavage of type IpCcollagen with procollagen C-proteinase. Fibrils formed at 37 degrees C had highly tapered and symmetrical pointed tips. The pattern of cross-striations in the pointed tips indicated that all the molecules were oriented so that the N-termini were directed towards the tip. At 29 degrees C and 32 degrees C, the fibrils formed were thicker. One end of fibrils formed at 29 degrees C was blunt, and the other was pointed. Growth of the fibrils was exclusively from pointed tips. Occasionally a spear-like projection appeared at a blunted end. The spear-like projection then became a new pointed tip for growth in the opposite direction. The results suggested a model for fibril growth with at least three distinct binding sites for monomers. In the model, the pointed tip is the site with the highest affinity for the binding of monomers and most probably defines the critical concentration for fibril assembly. The main shaft of the fibril is a site with very low affinity for binding. The blunted end defines a low-affinity binding site where monomers can bind in opposite orientation to produce growth from a new pointed end.

Bone morphogenic protein-1 (BMP-1) was originally identified as one of several BMPs that induced new bone formation when implanted into ectopic sites in rodents. BMP-1, however, differed from other BMPs in that it its structure was not similar to transforming growth factor 13. Instead, it had a large domain homologous to a metalloendopeptidase isolated from crayfish, an epidermal growthfactor-like domain, and three regions of internal sequence homology referred to as CUB domains. Therefore, BMP-1 was a member of the "astacin families" of zinc-requiring endopeptidases. Many astacins have been shown to play critical roles in embryonic hatching, dorsal/ventral patterning, and early developmental decisions. Here, we have obtained amino acid sequences and isolated cDNA clones for procollagen Cproteinase (EC 3.4.24.19), an enzyme that is essential for the processing of procollagens to fibrillar collagens. The results demonstrate that procollagen C-proteinase is identical to BMP-1.Bone morphogenic protein (BMP) was originally identified by Urist (1) and then by Reddi and Huggins (2) as an activity found in extracts of demineralized bone that induced new bone formation when implanted into ectopic sites in rodents. In 1988, Wozney and coworkers (3) obtained partial amino acid sequences of several components with bone morphogenic activity and used the sequence information to isolate three cDNA clones that they named BMP-1, BMP-2A, and BMP-3. On the basis of their structural similarity, BMP-2A and BMP-3 were identified as members of the transforming growth factor f3 (TGF-13) superfamily. Subsequently, five additional BMPs that were also similar to the TGF-,B superfamily were identified (4, 5). BMP-1, however, was apparently isolated as a complex with the other BMPs because it differed in structure from TGF-f3. It contained a large domain homologous to a metalloendopeptidase isolated from crayfish (6); an epidermal growth factor (EGF)-like domain; and three regions of internal sequence homology referred to as CUB domains because they are found in the complement components Clr/Cls, the sea urchin protein Uegf, and BMP-1 (7). The metalloendopeptidase from crayfish is now recognized as one of the simplest members of the "astacin family" of over 17 similar zinc-requiring endopeptidases (7-10).

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Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.